title: Second-site compensatory mutations of HIV-1 capsid mutations.
abstract: The human immunodeficiency virus (HIV) capsid (CA) protein assembles into a hexameric lattice that forms the mature virus core. Contacts between the CA N-terminal domain (NTD) of one monomer and the C-terminal domain (CTD) of the adjacent monomer are important for the assembly of this core. In this study, we have examined the effects of mutations in the NTD region associated with this interaction. We have found that such mutations yielded modest reductions of virus release but major effects on viral infectivity. Cell culture and in vitro assays indicate that the infectivity defects relate to abnormalities in the viral cores. We have selected second-site compensatory mutations that partially restored HIV infectivity. These mutations map to the CA CTD and to spacer peptide 1 (SP1), the portion of the precursor Gag protein immediately C terminal to the CTD. The compensatory mutations do not locate to the molecularly modeled intermolecular NTD-CTD interface. Rather, the compensatory mutations appear to act indirectly, possibly by realignment of the C-terminal helix of the CA CTD, which participates in the NTD-CTD interface and has been shown to serve an important role in the assembly of infectious virus.
authors.affiliation: Department of Microbiology, Oregon Health & Science University, Mail Code L220, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA.
authors.forename: Colleen M
authors.initials: CM
authors.lastname: Noviello
authors.forename: Claudia S
authors.initials: CS
authors.lastname: López
authors.forename: Ben
authors.initials: B
authors.lastname: Kukull
authors.forename: Henry
authors.initials: H
authors.lastname: McNett
authors.forename: Amelia
authors.initials: A
authors.lastname: Still
authors.forename: Jacob
authors.initials: J
authors.lastname: Eccles
authors.forename: Rachel
authors.initials: R
authors.lastname: Sloan
authors.forename: Eric
authors.initials: E
authors.lastname: Barklis
mesh_terms: D036022:Capsid Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D055503:Protein Multimerization; D013489:Suppression, Genetic; D014774:Virulence; D057074:Virus Release
chemical_list: D036022:Capsid Proteins; D050505:Mutant Proteins